HIV Controllers: A Homogeneous Group of HIV-1—Infected Patients with Spontaneous Control of Viral Replication

INSERM E-0109, Faculté de Médecine Paris-Sud, Université Paris XI, Service de Santé Publique, Bicêtre, France.
Clinical Infectious Diseases (Impact Factor: 8.89). 11/2005; 41(7):1053-6. DOI: 10.1086/433188
Source: PubMed


We identified a total 15 patients who have maintained undetectable plasma HIV RNA loads without antiretroviral treatment for >10 years from cohorts of 1300 and 1551 patients infected with human immunodeficiency virus (HIV). These 15 patients, whom we have referred to as "HIV controllers," are characterized by a low HIV DNA load in peripheral blood mononuclear cells and by a strong HIV-specific immune response.

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    • "Biological data analysis underlined the possibility that genetics played a role in this unusual occurrence , in particular the possible overrepresentation of certain Human Leucocyte Antigen (HLA) alleles (Deeks & Walker, 2007). HIV controllers are rare, accounting for less than 1% of HIV-infected patients (Lambotte et al., 2005). They have been identified in Europe, United States, Japan, and elsewhere, and the modes of HIV transmission in the population have been comprehensively described. "
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    ABSTRACT: Some people living with HIV spontaneously control the virus without antiretroviral treatment. They are called HIV Controllers and their status places them at the limits of bio-clinical normality. The objective of this study was to investigate HIV Controllers’ beliefs and representations of their individual trajectories using a qualitative approach. Fourteen HIV Controllers were interviewed. Vertical analysis focused on examining how interviewees’ specific beliefs and representational processes help these patients adapt to their particular situation. Horizontal analysis focused on how patients’ biographic trajectories and identity positioning help them make sense of their situation. Results highlighted that perceiving oneself to be healthy or ill was linked to change or a lack of change in terms of disease perception, beliefs and representations, when seropositivity was announced. This study of social representations and the processes involved provides crucial elements for health professionals caring for HIV Controllers.
    Full-text · Article · Dec 2015 · Qualitative Health Research
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    • "Pediatric long-term nonprogressors (LTNPs) are individuals infected with HIV-1 who maintain a suppressed viral load, which refers to either an undetectable viral load (HIV RNA <20 to 75 copies/mL) or a low-detectable HIV-RNA viral load (typically HIV RNA <200 copies/mL), depending on the sensitivity of the HIV RNA assay that is used, despite not being on ART [2]. The clinical relevance of the LTNP classification is not well understood, as some patients remain virologically suppressed, while others have gone on to develop AIDS. "
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    ABSTRACT: Patients infected with HIV are best categorized along a continuum from rapid progressors to HIV long-term nonprogressors. Long-term nonprogressors (LTNPs) are those in which AIDS develop many years after being infected with HIV, often beyond the 10-year mark, and represent 15-20% of the HIV infected patients. Many of these patients are able to control their infection and maintain undetectable viral loads for long periods of time without antiretroviral therapy. After a comprehensive literature search, we found extensive data related to HIV LTNPs in the adult population; however, very limited data was available related to LTNPs within the pediatric population. We present a case of pediatric HIV LTNPs, perinatally infected patient with undetectable viral loads, despite never receiving ART. Although there are not many instances of LTNPs among children, this child may be one, though she had intermittent viremia. She has continued to manifest serologic evidence of infection, with yearly ELISA and western blot positive tests. Based on the viral fitness studies that were performed, this case exemplifies an adolescent LTNP.
    Full-text · Article · Aug 2014
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    • "HIV-1 infected controllers maintain durable viral suppression without anti-retroviral therapy (ART) and have generally been defined as either having undetectable HIV-1 RNA levels using conventional assays (elite controllers) or having low but detectable levels of viral replication below 2000 copies viral RNA/ml (viremic controllers) [1], [2], [3], [4], [5], [6]. Although mechanisms of elite control have been widely studied [7], [8], [9], [10], [11], [12], [13], the immunological factor(s) associated with host control in presence of low but detectable viral replication in viremic controllers remains of considerable interest. "
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    ABSTRACT: HIV-1 infected viremic controllers maintain durable viral suppression below 2000 copies viral RNA/ml without anti-retroviral therapy (ART), and the immunological factor(s) associated with host control in presence of low but detectable viral replication are of considerable interest. Here, we utilized a multivariable analysis to identify which innate and adaptive immune parameters best correlated with viral control utilizing a cohort of viremic controllers (median 704 viral RNA/ml) and non-controllers (median 21,932 viral RNA/ml) that were matched for similar CD4+ T cell counts in the absence of ART. We observed that HIV-1 Gag-specific CD8+ T cell responses were preferentially targeted over Pol-specific responses in viremic controllers (p = 0.0137), while Pol-specific responses were positively associated with viral load (rho = 0.7753, p = 0.0001, n = 23). Viremic controllers exhibited significantly higher NK and plasmacytoid dendritic cells (pDC) frequency as well as retained expression of the NK CD16 receptor and strong target cell-induced NK cell IFN-gamma production compared to non-controllers (p<0.05). Despite differences in innate and adaptive immune function however, both viremic controllers (p<0.05) and non-controller subjects (p<0.001) exhibited significantly increased CD8+ T cell activation and spontaneous NK cell degranulation compared to uninfected donors. Overall, we identified that a combination of innate (pDC frequency) and adaptive (Pol-specific CD8+ T cell responses) immune parameters best predicted viral load (R2 = 0.5864, p = 0.0021, n = 17) by a multivariable analysis. Together, this data indicates that preferential Gag-specific over Pol-specific CD8+ T cell responses along with a retention of functional innate subsets best predict host control over viral replication in HIV-1 infected viremic controllers compared to chronically-infected non-controllers.
    Full-text · Article · Jul 2014 · PLoS ONE
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